Latest News from Around the CTSA Program Consortium

Medical University of South Carolina researchers Shikhar Mehrotra, Ph.D. and Xue-Zhong Yu, M.D. talking to each other the lab Emma Vought, Medical University of South Carolina
Natural Antioxidant Helps Improve Immune-based Therapies by Modulating T-cells

South Carolina Clinical & Translational Research Institute

With support from the South Carolina Clinical & Translational Research (SCTR) Institute, Medical University of South Carolina researchers Shikhar Mehrotra, Ph.D. (left)and Xue-Zhong Yu, M.D. (right)have shown that immune-based treatments, such as adoptive T-cell therapy and hematopoietic stem cell transplantation (HSCT), can be improved by modulating T-cells with thioredoxin, a powerful, naturally occurring antioxidant molecule. 

In the Journal of Biological Chemistry, Mehrotra reports that thioredoxin extends the life of adoptive T-cells by neutralizing toxic reactive oxygen molecules (ROS), overcoming a major drawback of this cancer immunotherapy. Mehrotra received SCTR pilot project funding.

Yu, who studies the development of graft-versus-host disease (GVHD) after HSCT, used a mouse model to test the effect of thioredoxin on donor T-cells. He reports in the Journal of Clinical Investigation that thioredoxin decreased toxic ROS in donor T-cells and made them less reactive to the patient’s healthy tissues, thereby preventing GVHD. Co-authors of the article included SCTR TL1 scholars.

July 10, 2019

Photograph by Sarah Pack, Medical University of South Carolina
Improving health outcomes with a little help from our friends—and artificial intelligence

South Carolina Clinical & Translational Research Center

The National Academy of Medicine has called for physicians to document social isolation in the electronic health record (EHR), because it can affect health outcomes. However, social isolation cannot be entered as coded data in current EHRs but only mentioned in clinical notes, which have historically been unintelligible to computers.  Medical University of South Carolina (MUSC)  investigators have trained natural language processing software to search clinical notes and identify socially isolated patients with 90 percent accuracy. MUSC owes its expertise in NLP in part to the NCATS-funded South Carolina Clinical & Translational (SCTR) Institute, a Clinical and Translational Science Award hub housed at MUSC. The NLP strategy developed by the MUSC team can be applied to other social determinants of health, particularly those that cannot be entered as coded data, and to other diseases. The team is already using NLP to identify patients with financial insecurity and alcohol abuse.

 

 

May 20, 2019

Medical University of South Carolina
Restoring this enzyme’s function protects against heart disease in lupus and beyond

South Carolina Clinical & Translational Research Institute at the Medical University of South Carolina

Patients with lupus are on average seven to nine times more likely to develop heart disease than the general population.

A research team at the Medical University of South Carolina (MUSC) led by Jim C. Oates, M.D., director of the Division of Rheumatology & Immunology, has shown that the enzyme responsible for nitric oxide production stops working properly when exposed to serum from lupus patients and that its function can be restored by administration of L-sepiapterin.

Nitric oxide is thought to be protective against heart disease.

The team collected serum samples from a cohort of African American patients, specifically Gullah patients, with lupus. The Research Nexus Research Center of the South Carolina Clinical & Translational Research (SCTR) Institute at MUSC helped the research team collect study samples from control volunteers and process samples from study patients and control volunteers.

Their findings, published by Lupus Science & Medicine, provide proof of concept that the enzyme could be a therapeutic target for heart disease in lupus.

March 26, 2019

Medical University of South Carolina
Potential therapeutic target for lung fibrosis identified

Medical University of South Carolina --South Carolina Clinical and Translational Research Institute

No current treatments reverse or stop lung fibrosis — scarring of the lung that makes it difficult to breathe. Medical University of South Carolina researchers report in Frontiers in Endocrinology that  they have identified a potential therapeutic target for lung fibrosis. The protein is an attractive target because it exerts its profibrotic influence earlier than other known profibrotic factors and increases their levels. Inhibiting it could also dampen their profibrotic effects, potentially helping curb disease progression in these patients. This important translational discovery was made possible by the South Carolina Clinical and Translational Research (SCTR) Institute’s TL1 predoctoral training program, which instills in graduate students the skills they will need to translate their basic science research to the clinic.  Xinh Xinh Nguyen, first author on the article, is a TL1 trainee, and Dr. Carol Feghali-Bostwick, the senior author,  is her mentor and the associate TL1 program director. Read more.

December 19, 2018

Medical University of South Carolina
Targeting sepsis, the leading cause of ICU deaths, with a nanocarrier-delivered microRNA

South Carolina Clinical and Translational Research Institute, Medical University of South Carolina

One in three patients who die in the U.S. dies of sepsis, according to the Centers for Disease Control and Prevention. It is one of the leading causes of death in ICUs and the most expensive condition that hospitals treat.

Researchers at the Medical University of South Carolina (MUSC) report in Inflammation that sepsis outcomes in a preclinical model significantly improved when a microRNA (miRNA), specifically miR-126, which is known to protect against sepsis, was delivered via a nanocarrier. Almost 67 percent of mice treated with one of the nanocarrier/miR-126 complexes were still alive at seven days vs. just 25 percent of untreated mice.

"The exciting part is that we can use nanoparticles as a delivery system to carry microRNAs. It's feasible--we can do this," says Hongkuan Fan, Ph.D., senior author of the article and an assistant professor in the Department of Pathology and Laboratory Medicine at MUSC who studies vascular dysfunction in sepsis. Joy N. Jones Buie, Ph.D., MSCR, a postdoctoral fellow at MUSC, was first author on the publication. The researchers received voucher funding from the South Carolina Clinical and Translational Research Institute, a CTSA hub.

December 03, 2018

Dr. James Chou (left) and Dr. Sherine Chan (right) are the founders of Neuroene Therapeutics Dr. James Chou (left) and Dr. Sherine Chan (right) are the founders of Neuroene Therapeutics
Neuroene Therapeutics awarded $1.5M to develop anti-seizure compound for epilepsy

Medical University of South Carolina --South Carolina Clinical and Translational Research Institute

Neuroene Therapeutics, a start-up company founded by mitochondrial biologist Sherine S. L. Chan, Ph.D. and medicinal chemist C. James Chou, Ph.D. of the Medical University of South Carolina, has received a $1.5 million NIH Phase II Small Business Innovation Research grant to optimize vitamin K analogues that could improve seizure control in patients with drug-resistant epilepsy.

Early testing of these vitamin K analogues by the MUSC investigators with pilot funding from the South Carolina Clinical and Translational Research Institute, a Clinical and Translational Science Awards hub funded by the National Institutes of Health, showed significantly reduced seizure activity with little toxicity in a zebrafish model. Testing in mouse seizure models at the National Institute of Neurological Disorders and Stroke Anticonvulsant Screening Program confirmed those findings. Chan and Chou established Neuroene Therapeutics in 2015 and received a patent on their lead compounds earlier this year. The current SBIR award will enable additional testing of the compounds’ efficacy and safety and the identification of a lead compound to take forward into clinical trial.

October 29, 2018

Photograph by Emma Vought
Leukogene Therapeutics receives funding to develop compound for resistant multiple myeloma

Medical University of South Carolina --South Carolina Clinical and Translational Research Institute

A $2 million phase 2 Small Business Technology Transfer (STTR) grant to optimize a promising new compound that has shown efficacy in preclinical studies against treatment-resistant multiple myeloma has been awarded to a Medical University of South Carolina (MUSC) startup company, Leukogene Therapeutics, Inc., in collaboration with MUSC researcher and company founder, Nathan G. Dolloff, Ph.D. Dolloff and his team will use the STTR award to further develop the new compound into a drug that could be used with proteasome inhibitors in treatment-resistant multiple myeloma.While proteasome inhibitors kill cancer cells by preventing the breakdown of proteins, Dolloff's compound targets instead their synthesis, preventing proper folding, which is essential to protein function. Normally, unfolded or misfolded proteins would then be targeted to the proteasome for degradation to avoid the build-up of these dysfunctional proteins. However, in the presence of proteasome inhibitors, the breakdown is blocked, leading to the build-up of toxic misfolded proteins.In principle, the compound developed by Dolloff could offer a one-two punch when administered together with proteasome inhibitors.

August 30, 2018

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